Hydrazine → N-[(1S)-2-amino-1-(cyclohexyl methyl)ethyl]-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxamide

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To a solution of 4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-N-{(1S)-2-cyclohexyl-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}-5-methyl-2-thiophenecarboxamide (231 mg, 0.44 mmol) in tetrahydrofuran (2.20 ml) and methanol (2.20 ml) at 25° C. was added hydrazine (0.14 ml, 4.40 mmol) dropwise. After 12 h, the solution was concentrated, dry loaded onto silica and purified by column chromatography (5% MeOH in DCM (1% NH4OH)). The free base was then transferred to the HCl salt adding excess 4M HCl in dioxane (1 ml) to the residue in MeOH (2 ml) affording the HCl salt of N-[(1S)-2-amino-1-(cyclohexyl methyl)ethyl]-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5-methyl-2-thiophenecarboxamide (124 mg, 0.27 mmol, 60% yield) as a yellow solid: LCMS (ES) m/z=394, 396 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.51 (br. s., 1H) 7.97 (br. s., 3H) 7.86 (s, 1H) 7.70 (s, 1H) 4.24-4.26 (m, 1H) 3.71 (s, 3H) 2.90-2.99 (m, 2H) 2.36 (s, 3H) 1.75-1.79 (m, 1H) 1.61 1.64 (m, 4H) 1.48-1.51 (m, 1H) 1.31-1.36 (m, 2H) 1.10-1.14 (m, 2H) 0.91-0.94 (m, 2H).

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